U.S. patent number 6,875,754 [Application Number 09/936,748] was granted by the patent office on 2005-04-05 for use of water-soluble .beta.-(1,3) glucans as agents for producing therapeutic skin treatment agents.
This patent grant is currently assigned to Biotec ASA. Invention is credited to Achim Ansmann, Rolf E. Engstad, Bernd Fabry, Ute Griesbach, Rolf Wachter.
United States Patent |
6,875,754 |
Griesbach , et al. |
April 5, 2005 |
Use of water-soluble .beta.-(1,3) glucans as agents for producing
therapeutic skin treatment agents
Abstract
The invention relates to the use of water soluble .beta.-(1,3)
glucans, which are essentially free from (1,6) links as active
ingredients agents for producing therapeutic skin treatment agents.
Said products strengthen the skin's immune system, counteract the
formation of wrinkles and can be used to treat psoriasis and
eczemic conditions.
Inventors: |
Griesbach; Ute (Dusseldorf,
DE), Wachter; Rolf (Dusseldorf, DE),
Ansmann; Achim (Erkrath, DE), Fabry; Bernd
(Korschenbroich, DE), Engstad; Rolf E. (Tromso,
NO) |
Assignee: |
Biotec ASA (Tromso,
NO)
|
Family
ID: |
7900739 |
Appl.
No.: |
09/936,748 |
Filed: |
February 4, 2002 |
PCT
Filed: |
March 03, 2000 |
PCT No.: |
PCT/EP00/01830 |
371(c)(1),(2),(4) Date: |
February 04, 2002 |
PCT
Pub. No.: |
WO00/54742 |
PCT
Pub. Date: |
September 21, 2000 |
Foreign Application Priority Data
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Mar 12, 1999 [DE] |
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199 11 054 |
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Current U.S.
Class: |
514/54; 514/23;
514/863; 514/887; 536/123.1; 536/123.12; 536/4.1 |
Current CPC
Class: |
A61K
8/73 (20130101); A61K 31/716 (20130101); A61Q
19/00 (20130101); A61Q 19/08 (20130101); A61K
31/716 (20130101); A61K 2300/00 (20130101); Y10S
514/863 (20130101); Y10S 514/887 (20130101) |
Current International
Class: |
A61K
8/72 (20060101); A61K 8/73 (20060101); A61Q
19/08 (20060101); A61Q 19/00 (20060101); A61K
031/716 (); A61K 031/715 () |
Field of
Search: |
;514/54,887,863,23
;536/4.1,123.1,123.12 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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WO 9530022 |
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Nov 1995 |
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EP |
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WO 9840082 |
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Sep 1998 |
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EP |
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3204804 |
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Sep 1991 |
|
JP |
|
Other References
Mansell PWA: "Polysaccharides in Skin Care", Cosmetics and
Toiletries, Wheaton, Illinois, vol. 109, No. 9, Sep. 1, 1994. .
"Kosmetikjahrbuch 1998", Verlag fur Chemische Industry, H.
Ziolkowsky GMBH, Augsburg..
|
Primary Examiner: Barts; Samuel
Assistant Examiner: Henry; Michael C.
Attorney, Agent or Firm: Ladas & Parry
Parent Case Text
This is the National Phase Application of PCT/EP00/01830 filed Mar.
3, 2000.
Claims
What is claimed is:
1. A method of treating skin conditions or skin diseases comprising
applying to the skin a preparation comprising water soluble
.beta.-(1,3) glucans, which have intact .beta.-(1,3) side chains
and are free from repetitive .beta.-(1,6) linkages, as active
substances.
2. The method according to claim 1, wherein the glucans are used in
amounts of 0.1% to 25% by weight based on the preparation.
3. The method of claim 1 wherein the skin conditions or skin
diseases are selected from the group consisting of wrinkles,
cellulitis, cradle cap, psoriasis, seborrheic dermatitis, seborrhea
sicca, seborrhea oleosa, psoriasis vulgaris, ichtyoses and UV
erythemas.
4. The method of claim 3 wherein the skin condition is
wrinkles.
5. The method of claim 3 wherein the skin condition is UV
erythemas.
6. A glucan for use in a therapeutic composition for treatment of
skin conditions or skin diseases, wherein said glucan comprises
water soluble .beta.-(1,3) glucans, which have intact .beta.-(1,3)
side-chains and are free from repetitive .beta.-(1,6) linkages.
7. The glucan of claim 6, wherein the said glucans are based on
yeast of the family Saccharomyces.
8. The glucan of claim 6, wherein said glucans are obtained by
contacting glucans with .beta.-(1,3) and .beta.-(1,6) linkages with
.beta.-(1,6) glucanases.
9. The glucan of claim 8, wherein said glucanases are based on
Trichoderma harzianum.
10. The glucan of claim 6, wherein said glucans are used in amounts
of 0.1% to 25% by weight relative to the therapeutic
composition.
11. The glucan of claim 6, wherein the skin conditions or skin
diseases are selected from the group consisting of wrinkles,
cellulite, cradle cap, psoriasis, seborrheic dermatitis, seborrhea
sicca, seborrhea oleosa, psoreasis vulgaris, ichtyoses and UV
erythema.
12. The glucan of claim 11, wherein the skin condition is
wrinkles.
13. The glucan of claim 11, wherein the skin condition is UV
erythemas.
14. A glucan for use in a therapeutic composition for treatment of
skin aging, wherein said glucan comprises water soluble
.beta.-(1,3) glucans, which have intact .beta.-(1,3) side-chains
and are free from repetitive .beta.-(1,6) linkages.
15. The glucan of claim 14, wherein said glucans are based on yeast
of the family Saccharomyces.
16. The glucan of claim 14, wherein said glucans are obtained by
contacting glucans with .beta.-(1,3) and .beta.-(1,6) linkages with
.beta.-(1,6) glucanases.
17. The glucan of claim 16, wherein said glucanases are based on
Trichoderma harzianum.
18. The glucan of claim 14, wherein said glucans are used in
amounts of 0.1% to 25% by weight relative to the therapeutic
composition.
19. The method of treating aging of the skin comprising applying to
the skin a preparation comprising water soluble .beta.-(1,3)
glucans, which have intact .beta.-(1,3) side chains and are free
from repetitive .beta.-(1,6) linkages as active substances.
20. The method according to claim 19, wherein the glucans are used
in amounts of 0.1% to 25% by weight based on the preparation.
Description
FIELD OF THE INVENTION
The invention relates to the use of specific water soluble
.beta.-(1,3) glucans as active agents for combating the formation
of wrinkles in the skin as well as skin diseases such as for
example dandruff tetter, psoriasis or UV erythemas.
PRIOR ART
The formation of wrinkles caused by increasing age is induced
through the degradation of different macro molecules such as for
example elastin and collagen, which are responsible for the
elastases. Many inflammatory skin diseases, such as for example
psoriasis or UV erythema, can also be causatively be linked to an
increased concentration of serine proteases, such as e.g. elastase
in the upper skin areas [see R. Voegeli et al. in Cosm. Toil. 111,
51(1996)].
The formation of wrinkles in the skin is normally not counteracted
by means of physiological active principles, but by means of
cosmetic agents. Many so-called "anti-aging products" contain
liposomes loaded with water or aqueous active agents, which through
the fat layer of the skin are reaching the epidermis, where they
gradually dissolve and through continuous water release compensate
the skin recesses and regulate the moisture content of the skin.
However, this effect is no combat against the causes, but only has
a so-called "repairing effect", which only lasts for a short period
of time.
In contrast to this pure cosmetic use, cytostatic active agents are
e.g. used for the abatement of psoriasis, such as selenium sulfide,
cadmium sulfide, zinc pyrithion or corticosteroid, the medical
effect of which resides e.g. in a reduction of the mitose activity
in the basal membrane. However, because of the known side effects
these substances should not be used over extended periods of time.
Further it is possible to alleviate, but not healing, psoriasis by
means of antiseptic active agents, such as for example selenium
oxide, salicylic acid, pyrithione derivatives, hexachlorophene or
quaternary ammonium compounds or by means of cell dissolving and
fat removing active substances such as for example benzoy peroxide
or tar extracts.
The use of specific polysaccharides as agents against the skin
aging is also known from prior art. It has for example been
proposed in U.S. Pat. No. 5,223,491 to use a carboxymethylated
.beta.-1,3 glucan, which has been extracted from the yeast fungi
Saccharomyces cerevisiae, for topical use. However, the glucan is
insoluble in water and can therefore only be formulated with large
difficulties.
In the European patent application EP-A1 0463540 (Taito) the use of
glucans against viruses is described. According to the teachings in
the two papers DE-A1 3744345 (Lomapharm) and EP-B1 0175667 (Larm)
glucans are only suited for stimulation of the activity of
macrophages. The pharmaceutical effect of different glucans is
further known from the two European patent applications EP-A1
045338 (Debat) and EP-A1 0561408 (Kaken). The object of the
European patent EP-B1 0500718 (Donzis) is the use of water
insoluble .beta.-(1,3) glucans, which have been obtained from the
cell walls of yeasts, for revitalisation of the skin.
Also known from the prior art are very different solutions known
for smoothing of the skin and strengthening of the barrier function
from a cosmetic or medical view, which only solve a part of the
problem and which may have strong side effects. Especially
reference is made to the international patent application WO
98/40082 (Henkel), wherein the use of water soluble .beta.-(1,3)
glucans as active agents for the skin treatment is described. These
glucans, which preferably are schizopyhallan or krestin, i.e.
extracts of fungi, have in practice not shown to be sufficiently
effective. The complex task of the invention was therefore further
to provide active agents which could be used against formation of
wrinkles in the skin (cosmetic effect) as well as skin diseases
(medical effect), and which can be both dermatological and
toxicological tolerated and which improve the prior art, as
described in WO 94/40082.
DESCRIPTION OF THE INVENTION
The object of the invention is the use of water soluble
.beta.-(1,3) glucans, which are substantially free from (1,6)
linkages, as active agents for preparation of therapeutical agents
for skin treatment and skin vitalization, especially for
manufacturing of agents which at the same time work against skin
aging and formation of wrinkles erythemas and which at the same
time stimulate the growth of cells.
Surprisingly it was found that water soluble .beta.-glucans which
practically do not have (1,6) linkages, in the Langerhans cells in
the deeper skin layers initiate an immuno modulation, whereby the
special cytokines are produced and which are significantly superior
to the known glucans of the prior art (according to WO 98/40082),
which have a significant amount of (1,6) linkages.
Water Soluble .beta.-(1,3) Glucans
The term glucans is intended to mean homopolysaccharides based on
glucose. Depending on sterical linking there is a difference
between .beta.-(1,3), .beta.-(1,4) and .beta.-(1,6) glucans.
.beta.-(1,3) Glucans normally show a helical structure, whereas
glucans with a (1,4) linkage generally have a linear structure. The
.beta.-glucans of the invention have a (1,3) structure, i.e. they
are substantillay free from undesired (1,6) linkages. Preferably
such .beta.-(1,3) glucans are used where the side chains
exclusively show (1,3) linkages. Especially the agents contain
glucans which are obtained on the basis of yeast from the family
Sacchaomyces, especially Saccharomyces cerevisiae. Glucans of this
type are available in technical amounts according to known methods.
The international patent application WO 95/30022 (Biotec-Mackzymal)
describes e.g. a method for producing such substances, wherein
glucans with .beta.-(1,3) and .beta.-(1,6) linkages are brought in
contact with .beta.-(1,6) glucanases in such a way, that
practically all .beta.-(1,6) linkages are loosened. Preferably used
for the manufacture of these glucans are glucanases based on
Trichodermia harzianum. As to the manufacture and availability of
the glucans contained in these agents, reference is made to the
above cited publication.
Commercial Applicability
For the purpose of the invention the water soluble .beta.-(1,3)
glucans find use as active agents for manufacturing cosmetic and/or
pharmaceutical preparations. Typical examples of such agents are
skin care agents such as for example anti-wrinkling cremes,
anti-cellulitis cremes or sun protection lotions as well as
ointments for treating skin diseases such as for example cradle
cap, psoriasis, seborrheic dermatitis, seborrhea sicca, seborrhea
oleosa, psoriasis vulgaris, ichtyoses or UV erythemas. Normally the
water soluble .beta.-glucans can be used in amounts of 0.1 to 25,
preferably 0.5 to 15 and especially 1 to 5% by weight, based on the
agents. The agents can further as additional auxiliary and
additional agents contain mild surfactants, oil bodies,
emulsifiers, hyperfatting agents, pearl lustre waxes, consistency
substances, thickening agents, polymers, silicon compounds, fats,
waxes, stabilizing agents, biogenic active substances, deodorants,
agents against dandruff, film forming agents, swelling agents, UV
light protection factors, antioxidants, inorganic colour pigments,
hydrotropes, preservatives, insect repellents, self tanning agents,
solubilizing agents, perfume oils, colouring agents and such
like.
Typical examples of suitable mild, i.e. especially skin compatible
surfactants are fatty alcohol polyglycol ether sulphates,
monoglyceride sulphates, mono- and/or dialkyl sulfosuccinates,
fatty acid isethionates, fatty acid sarcosinates, fatty acid
taurides, fatty acid glutamates, .alpha.-olefine sulphonates,
ethercarboxylic acids, alkyl oligoglucosides, fatty acid
glucamides, alkylamido betaines and/or protein fatty acid
condensates, the last mentioned preferably based on wheat
proteins.
As oil bodies use can be made of for example Guerbet alcohols based
on fatty alcohols with 6 to 18, preferably 8 to 10 carbon atoms,
esters of linear C.sub.6 -C.sub.22 fatty acids with linear C.sub.6
-C.sub.22 fatty alcohols, esters of branched C.sub.6 -C.sub.13
carboxylic acids with linear C.sub.6 -C.sub.22 fatty alcohols, such
as e.g. myristyl myristate, myristyl palmitate, myristyl stearate,
myristyl isostearate, myristyl oleate, myristyl behenate, myristyl
erucate, cetyl myristate, cetyl palmitate, cetyl stearate, cetyl
isostearate, cetyl oleate, cetyl behenate, cetyl erucate, stearyl
myristate, stearyl palmitate, stearyl stearate, stearyl
isostearate, stearyl oleate, stearyl behenate, stearyl erucate,
isostearyl myristate, isostearyl palmitate, isostearyl stearate,
isostearyl isostearate, isostearyl oleate, isosteayl behenate,
isostearyl oleate, oleyl myristate, oleyl palmitate, oleyl
stearate, oleyl isostearate, oleyl oleate, oleyl behenate, oleyl
erucate, behenyl myristate, behenyl palmitate, behenyl stearate,
behenyl isostearate, behenyl oleate, behenyl behenate, behenyl
erucate, erucyl myristate, erucyl palmitate, erucyl stearate,
erucyl isostearate, erucyl oleate, erucyl behenate and erucyl
erucate. In additon esters of linear C.sub.6 -C.sub.22 fatty acids
with branched alcohols, especially 2-ethylhexanol, esters of
hydroxycarboxylic acids with linear or branched C.sub.6 -C.sub.22
fatty alcohols, especially dioctyl malate, esters of linear and/or
branched fatty acids with polyvalent alcohols (such as e.g.
propylene glycol, dimeric diol or trimeric triol) and/or Guerbet
alcohols, triglycerides based on C.sub.6 -C.sub.10 fatty acids,
liquid mixtures of mono-/di-/triglycerides based on C.sub.6
-C.sub.18 fatty acids, esters of C.sub.6 -C.sub.22 fatty alcohols
and/or Guerbet alcohols with aromatic carboxylic acids, especially
benzoic acid, esters of C.sub.2 -C.sub.12 dicarboxylic acids with
linear or branched alcohols with 1 to 22 carbon atoms or polyols
with 2 to 10 carbon atoms and 2 to 6 hydroxyl groups, plant oils,
branched primary alcohols, substituted cyclohexanes, linear and
branched C.sub.6 -C.sub.22 fatty alcohol carbonates, Guerbet
carbonates, esters of benzoic acid with linear and/or branched
C.sub.6 -C.sub.22 alcohols (e.g. Finsolv.RTM. TN), linear or
branched, symmetrical or unsymmetrical dialkyl ethers with 6 to 22
carbon atoms in each alkyl group, ring opening products of
epoxydated fatty acid esters with polyols, silicone oils and/or
aliphatic or naphthenic hydrocarbons, such as e.g. squalan, squalen
or dialkyl cyclohexanes, can be used
As emulsifiers for example nonionic surfactants from at least one
of the following groups may be used: (1) Addition products of 2 to
30 moles ethylene oxide and/or 0 to 5 moles propylene oxide on
linear fatty alcohols with 8 to 22 C atoms, on fatty acids with 12
to 22 C atoms and on alkyl phenols with 8 to 15 C atoms in the
alkyl group; (2) C.sub.12/18 fatty acid mono- and -diesters of
addition products of 1 to 30 moles ethylene oxide and glycerol; (3)
glycerol mono- and diesters and sorbitan mono- and diesters of
saturated and unsaturated fatty acids with 6 to 22 carbon atoms and
their ethylene oxide addition products; (4) alkyl mono- and
oligoglycosides with 8 to 22 carbon atoms in the alkyl group and
their ethoxylated analogues; (5) addition products of 15 to 60
moles ethylene oxide on ricinus oil and/or hardened ricinus oil;
(6) polyol and especially polyglycerol esters, such as e.g.
polyglycerol polyricinoleate, polyglycerol poly-12-hydroxystearate
or polyglycerol dimerate isostearate, and also mixtures of
compounds from more of these classes of substances; (7) addition
products of 2 to 15 moles ethylene oxide on ricinus oil and/or
hardened ricinus oil; (8) partial esters based on linear, branched,
unsaturated or saturated C.sub.6/22 fatty acids, ricinolic acid and
12-hydroxy stearic acid and glycerol, polyglycerol, pentaerythrite,
dipentaerythrite, sugar alcohols (e.g. sorbitol), alkyl glucosides
(e.g. methyl glucoside, butyl glucoside, lauryl glucoside) as well
as polyglucosides (e.g. cellulose); (9) mono-, di- and
trialkylphosphates as well as mono-, di- and/or tri-PEG
alkylphosphates and their salts; (10) wool wax alcohols; (11)
polysiloxane/polyalkyl/polyether copolymers or corresponding
derivatives; (12) mixed esters of pentaerythrite, fatty acids,
citric acid and fatty alcohol according to DE 1165574 PS and/or
mixed esters of fatty acids with 6 to 22 carbon atoms, methyl
glucose and polyols, preferably glycerol or polyglycerol, (13)
polyalkylene glycols, as well as (14) glycerol carbonate.
The addition products of ethylene oxide and/or of propylene oxide
on fatty alcohols, fatty acids, alkyl phenols, glycerol mono- and
diesters as well as sorbitan mono- and -diesters of fatty acids or
on ricinus oil are known products which are commercially available.
They are mixtures of homologous substances, with average degree of
alkoxylation corresponding to the ratio of the amounts of the
substances ethylene oxide and/or propylen oxide and substrate, with
which the addition reaction is carried out. C.sub.12/18 fatty acid
mono- and -diesters of addition products of ethylene oxide on
glycerol are known from DE 2024051 PS as revertive fatting agents
for cosmetic preparations.
C.sub.8/18 alkyl mono- and oligoglycosides, their manufacture and
their use is known from prior art. Their preparation can especially
be carried out by reaction of glucose or oligosaccharides with
primary alcohols having 8 to 18 C atoms. With regard to the
glycoside residue both monoglycosides, where a cyclic sugar group
is glycosidic bond to the fatty alcohol, and oligomeric glycosides
with a degree of oligomerisation until preferably about 8, are
suitable. The degree of oligomerization is then a statistical mean
value, based on a distribution of homologues which is usual for
such products of technical quality.
Zwitterionic surfactants can also be used as emulsifiers. The term
zwitterionic surfactants is intended to mean such surface active
compounds which in their molecule have at least a quatenary
ammonium group and at least one carboxylate and one sulphonate
group. Especially suitable zwitterionic surfactants are the
so-called betaines such as the N-alkyl-N,N-dimethyl ammonium
glycinates, for example the coco alkyldimethyl ammonium glycinate,
N-acylaminopropyl-N,N-dimethyl ammonium glycinate, for example the
coco acylaminopropyl dimethyl ammonium glycinate, and
2-alkyl-3-carboxylmethyl-hydroxyethyl imidazoline with in each case
8 to 18 C atoms in the alkyl or acyl-groups, as well as the coco
acylaminoethyl hydroxyethylcarboxymethyl glycinate. Especially
preferred is that under the CTFA term cocamidopropyl betaine known
fatty acid amide derivative. Also suitable emulsifiers are
ampholytic surfactants. Ampholytic surfactants are such surface
active compounds which in addition to a C.sub.8/18 alkyl or acyl
group in the molecule at least contain a free amino group and at
least one --COOH or --SO.sub.3 H group and which can form inner
salts. Examples of suitable ampholytic surfactants are N-alkyl
glycines, N-alkyl propionic acids, N-alkyl aminobutyric acids,
N-alkyl iminodipropionic acids, N-hydroxyethyl-N-alkylamidopropyl
glycines, N-alkyltaurines, N-alkylsarcosines, 2-alkylaminopropionic
acids and alkylamino acetic acids with in each case about 8 to 18 C
atoms in the alkyl group. Especially preferable ampholytic
surfactants are the N-coco alkylamino propionate, the coco
acylamino ethylaminopropionate and the C.sub.12/18 acylsarcosine.
In addition to the ampholytic, also quaternary emulsifiers can be
used, of which ester salts of the type of esterquats, preferably
methylquaternised di-fatty acid triethanolamine ester salts, are
especially preferable.
As hyperfafting agents substances such as for example lanolin and
lecithin as well as polyethoxylated or acylated lanolin and
lecithin derivatives, polyol fatty acid esters, monoglycerides and
fatty acid alkanolamides can be used, whereby the last mentioned at
the same time act as foam stabilisers.
As exemplary pearl gloss waxes the following should be mentioned:
Alkylene glycolester, especially ethyleneglycol distearate; fatty
acid alkanolamides, especially coco fatty acid diethanolamide;
partial glycerides, especially stearic acid monoglyceride; esters
of polyvalent, possibly hydroxysubstituted carboxylic acids with
fatty alcohols with 6 to 22 carbon atoms, especially long chain
esters of tartaric acid; fat substances, such as for example fatty
alcohols, fatty ketones, fatty aldehydes, fatty ethers and fatty
carbonates, wherin the sum of carbon atoms is at least 24,
especially lauron and distearyl ethers; fatty acids such as stearic
acid, hydroxystearic acid or behenic acid, ring opening products of
olefine epoxides with 12 to 22 carbon atoms with fatty alcohols
with 12 to 22 carbon atoms and/or polyols with 2 to 15 carbon atoms
and 2 to 10 hydroxyl groups as well as their mixtures.
As consistency givers preferably use is made of fatty alcohols or
hydroxy fatty alcohols with 12 to 22 and preferably 16 to 18 carbon
atoms and additionally partial giycerides, fatty acids or hydroxy
fatty acids. A combination of these substances with alkyl
oligoglucosides and/or fatty acid-N-methyl glucamides with the same
chain length and/or polyglycerol-poly-12-hydroxy stearates.
Suitable thickening agents are for example types of aerosil
(hydrophilic silicic acids), polysaccharides, especially xanthan
gum, guar-guar, agar-agar, alginates and tyloses, carboxymethyl
celluloses and hydroxyethyl celluloses, as well as higher molecular
polyethylenglycol mono- and diesters of fatty acids, polyacrylates,
(e.g. Carbopols.RTM. from Goodrich or Synthalenes.RTM. from Sigma),
poly-acrylamides, polyvinyl alcohol and polyvinyl pyrrolidone,
surfactants such as for example ethoxylated fatty acid glycerides,
ester of fatty acids with polyols such as for example
pentaerythrite or trimethylolpropane, fatty alcohol ethoxytates
with narrow distribution of homologous or alkyl oligoglucosides as
well as electrolytes such as sodium chloride and ammonium
chloride.
Suitable cationic polymers are for example cationic cellulose
derivatives, such as e.g. a quaternized hydroxyethyl cellulose,
which is available under the name of Polymer JR 400.RTM. from
Amerchol, cationic starch, copolymers of diallyl ammonium salts and
acrylamides, quaternized vinylpyrrolidone/vinylimidazol polymers,
such as e.g. Luviquat.RTM. (BASF), condensation products of
polyglycols and amines, quaternized collagen polypeptides, such as
for example lauryl dimonium hydroxypropyl hydrolyzed collagen
(Lamequat.RTM.L/Grunau), quaternized wheat polypeptides,
polyethyleneimine, cationic silicone polymers, such as e.g.
amidomethicones, copolymers of adipic acid and dimethylamino
hydroxypropyl diethylenetriamine (Cartaretine.RTM./Sandoz),
copolymers of acrylic acid with dimethyl diallylammonium chloride
(Merquat.RTM. 550/Chemviron), polyamino polyamides, such as e.g.
described in FR 2252840 A, as well as their cross-linked water
soluble polymers, cationic chitin derivatives such as for example
quaternized chitosane, possibly micro crystalline distributed,
condensation products of dihalogen alkyls, such as e.g.
dibromobutane with bisdialkylamines, such as e.g.
bis-dimethylamino-1,3-propane, cationic guar-gum, such as e.g.
Jaguar.RTM. CBS, Jaguar.RTM. C-17, Jaguar.RTM. C-16 from Celanese,
quaternised ammonium salt polymers, such as e.g. Mirapol.RTM. A-15,
Mirapol.RTM. AD-1, Mirapol.RTM. AZ-1 from Miranol.
As exemplary anionic, zwitterionic, amphoteric and non-ionic
polymers the following can be used: Vinyl acetate/crotonic acid
copolymers, vinyl pyrrolidone/vinyl acrylate copolymers, vinyl
acetate/butyl maleate/isobornyl acrylate copolymers, methyl
vinylether/maleic acid anhydride copolymers and their esters,
non-cross-linked and with polyols cross-linked polyacrylic acids,
acrylamido propyltrimethyl ammonium chloride/acrylate copolymers,
octylacrylamide/methyl methacrylate/ tert.-butylaminoethyl
methacrylate/2-hydroxypropyl methacrylate copolymers,
polyvinylpyrrolidone, vinylpyrrolidone/vinylacetate copolymers,
vinylpyrrolidon/ dimethylamino ethylmethacrylate/vinyl caprolactam
terpolymers as well as possibly derivatized cellulose ethers and
silicones.
Suitable silicon compounds are for example dimethyl polysiloxane,
methylphenyl polysiloxane, cyclic silicones as well as amino, fatty
acid, alcohol, polyether, epoxy, fluorine, glycoside and/or alkyl
modified silicon compounds, which at room temperature can be in the
liquid as well as in the resin state. Further suitable are
simethicones, which are mixtures of dimethicones with an average
chain length of 200 to 300 dimethyl siloxane units and hydrogenated
silicates. A detailed survey of suitable volatile silicones can
also be found in Todd et al., Cosm. Toil. 91, 27 (1976).
Typical exemplary fats are glycerides, and as waxes natural waxes
among others, can be used, such as e.g. candelilla wax, carnauba
wax, Japan wax, espartogras wax, cork wax, guaruma wax, rice seed
oil wax, sugar cane wax, ouricury wax, montan wax, beeswax,
shellack wax, spermaceti, lanolin (wool wax), burzel fat, ceresin,
ozokerit (terrestrial wax), petrolatum, paraffin waxes, micro
waxes; chemically modified waxes (hard waxes), such as e.g.
montanester waxes, sasot waxes, hydrogenated yoyoba waxes as well
as synthetic waxes, such as e.g. polyalkylene waxes and
polyethylene glycol waxes.
As stabilizers metal salts of fatty acids, such as e.g. magnesium,
aluminium and/or zinc stearate or ricinoleate can be used.
As biogenic active substances should be understood for example
tocopherol, tocopherol acetate, tocopherol palmitate, ascorbic
acid, desoxy ribonucleic acid, retinol, bisabolol, allantoin,
phytantriol, panthenol, AHA acids, aminoacids, ceramides,
pseudoceramides, essential oils, extracts of plants and vitamin
complexes.
As deo active agents e.g. antiperspirants such as aluminium
chlorohydrate come into question. This agent is in the form of
colourless, hygroscopic crystals, which easily melt in air, and is
obtained through evaporation of solutions of aluminium chloride in
water. Aluminium chlorohydrate is used for manufacturing of
perspiration inhibiting and deodorising preparations and has
probably its effect through the partial closure of the perspiratory
gland by means of precipitation of proteins and/or polysaccharides
[see J.Soc. Cosm.Chem. 24 281 (1973)]. Under the trade name
Locron.RTM. of Hoechst AG, Frankfurt/FRG, an aluminium
chlorohydrate is for example on the market, which corresponds to
the formula [Al.sub.2 (OH).sub.5 Cl].2.5 H.sub.2 O, and use of this
is especially preferred (see J.Pharm.Pharmacol. 26 531 (1975)]. In
addition to the chlorohydrates also aluminium hydroxylactates as
well as acid aluminium/zirconium salts can be used. As further deo
active agents esterase inhibitors can be added. These are
preferably trialkyl citrates such as trimethyl citrate, tripropyl
citrate, triisopropyl citrate, tributyl citrate and especially
triethyl citrate (Hydagen.RTM. CAT, Henkel KGaA, Dusseldorf/FRG).
The substances inhibit the enzyme activity and thereby reduce the
formation of odours. Probably the free acid is thereby set free
through the cleavage of the citric acid ester, and this acid lowers
the pH value of the skin so much that the enzymes thereby are
inhibited. Further substances which can be used as estersase
inhibitors are sterol sulphates or phosphates, such as for example
lanosterol, cholesterol, campesterol, stigmasterol and sitosterol
sulphate or phosphate, Dicarboxylic acids and their esters, such as
for example glutaric acid, glutaric acid monoethylester, glutaric
acid diethylester, adipic acid, adipic acid monoethylester, adipic
acid diethylester, malonic acid and malonic acid diethylester,
hydroxycarboxylic acids and their esters, such as for example
citric acid, malic acid, tartaric acid or tartaric acid
diethylester. Antibacterial active substances, which influence the
germ flora and kill sweat destroying bacteria or inhibit their
growth, can also be contained in the pin preparations. Examples of
this are chitosan, phenoxyethanol and chlorohexidin gluconate. Also
5-chloro-2-(2,4-dichlorophen-oxy)-phenol has shown to have an
especially good effect, and this product is marketed under the
trade name Irgasan.RTM. by Ciba-Geigy, Basel/CH.
As anti dandruff agents climbazol, octopirox and zinc pyrethion can
be used. Useable film formation agents are for example chitosan,
microcrystalline chitosan, quaternary chitosan,
polyvinylpyrrolidon, vinylpyrrolidon/vinylacetate copolymers,
polymers of the acrylic acids, quaternary derivatives of cellulose,
collagen, hyaluronic acid or its salts and similar compounds. As
swelling agents for aqueous phases montmorillonite, clay mineral
substances, pemulen, as well as alkylmodified Carbopol types
(Goodrich) can be used. Further suitable polymers or swelling
agents can be found in the survey of R. Lochhead in Cosm. Toil.
108, 95 (1993).
UV light protection factors are e.g organic substances (light
protection filters) which by room temperature are in liquid or
crystalline form, and which are capable of absorbing ultraviolet
radiation and to set free the received energy in the form of
radiation with long wavelength, e.g. in the form of heat. UVB
filters can be soluble in oils or in water. As oil soluble
substances the following are mentioned as examples: 3-Benzyliden
camphor, respectively 3-benzylidene norcamphor and the derivatives
thereof, e.g. 3-(4-methylbenzylidene) camphor as described in EP-B1
0693471; 4-aminobenzoic acid derivatives, preferably
4-(dimethylamino) benzoic acid 2-ethylhexylester, 4-(dimethylamino)
benzoic acid 2-octylester and 4-(dimethylamino) benzoic acid
amylester; esters of cinnamonic acid, preferably 4-methoxy
cinnamonic acid 2-ethylhexylester, 4-methoxy cinnamonic acid
propylester, 4-methoxy cinnamonic acid isoamylester,
2-cyano-3,3-phenyl cinnamonic acid 2-ethythexylester (octocrylene);
esters of salicylic acid, preferably salicylic acid
2-ethylhexylester, salicylic acid 4-isopropyl benzylester,
salicylic acid homomenthylester;
derivatives of benzophenone, preferably 2-hydroxy4-methoxy
benzophenone, 2-hydroxy4-methoxy-4'-methyl benzophenone,
2,2'-dihydroxy4-methoxy benzophenone; esters of benzalmalonic acid,
preferably 4-methoxy benzmalonic acid 2-ethylhexyl ester, triazine
derivatives, such as e.g.
2,4,6-trianilino-(p-carbo-2'-ethyl-1'-hexyloxy)-1,3,5-triazine and
octyltriazone, as described in EP A1 0818450; propane-1,3-diones,
such as
e.g.1-(4-tert.-butylphenyl)-3-(4'-methoxy-phenyl)-propane-1,3-dion;
ketotricyclo(5,2,1,0)-decane derivatives, as described in EP-B1
06945521. As water soluble substances the following can be
mentioned: 2-Phenylbenzimidazol-5-sulphonic acid and the alkali,
alkaline earth, ammonium, alkylammonium, alkanolammonium and
glucammonium salts; sulphonic acid derivatives of benzophenones,
preferably 2-hydroxy-4-methoxybenzophenon-5-sulphonic acid and
their salts; sulphonic acid derivatives of 3-benzylidencamphen,
such as e.g. 4-(2-oxo-3-bornylidenmethyl)-benzene sulphonic acid
and 2-methyl-5-(2-oxo-bornyliden) sulphonic acid and their
salts.
As typical UV-A filters especially derivatives of benzoyl methane
comes in question, such as e.g.
.beta.-(4'-tert.-butylphenyl)-3-(4'-methoxyphenyl)propane-1,3-dion,
4-tert.butyl-4'-methoxydibenzoyl-methane (Parsol 1789), or
1-phenyl-3-(4'-isopropylphenyl-propane-1,3-dion. The UV-A and UV-B
filters can of course also be used in mixtures. In this case
combinations of octocrylene or camphor derivatives with butyl
methoxydibenzoylmethane are especially photosensitive.
In addition to the mentioned soluble substances also insoluble
light protection pigments can be used for this purpose, i.e. fine
disperse metal oxides or salts. Examples of suitable metal oxides
are especially zinc oxide and titanium dioxide and in addition
other oxides of iron, zirconium, silicon, manganese, aluminium and
cerium, as well as their mixtures. As salts silicates tall, barium
sulphate or zinc stearate can be used. The oxides and salts are
used in the form of the pigments for skin caring and skin
protecting emulsions and decorative cosmetics. The particles should
have an average diameter of less than 100 nm, preferably between 5
and 50 nm and especially between 15 and 30 nm. They can have a
spherical shape, but particles can also be used which have an
ellipsoidal form or else have a shape which differs from the
spherical shape. In sun protecting agents preferably so-called
micro or nano pigments are used. Preferably micronized zinc oxide
is used. Further suitable,UV light protection factors can be found
in the survey by P. Finkel in SOFW-Journal 122, 543 (1996).
Likewise suitable are herbal extracts with UV absorbing or
antioxidative properties.
In addition to the primary light protection substances also
secondary light protection substances of the antioxidant type find
use, which interrupt the photochemichal reaction chain, which is
initiated when UV radiation penetrates the skin. Typical examples
of such are amino acids (e.g. glycin, histidin, tyrosin,
tryptophan) and their derivatives, imidazoles (e.g. urocaninic
acid) and their derivatives, peptides such as D,L-camosine,
D-camosine, L-camosine and their derivatives (e.g. anserine),
carotinoides, carotine (e.g. .alpha.-carotin, .beta.-carotin,
lycopin) and their derivatives, chlorogenic acid and its
derivatives, liponic acid and its derivatives (e.g. dihydroliponic
acid), aurothioglucose, propylthiouracil and other thiols (e.g.
thioredoxin, glutathion, cystein, cystin, cystamine and their
glycosyl, n-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl,
palmitoyl, oleyl, .gamma.-linoleyl, cholesteryl and glyceryl
esters) as well as their salts, dilauryl thiodipropionate,
distearyl thiodipropionate, thiodipropionic acid and their
derivatives (esters, ethers, peptides, lipides, nucleotides,
nucleosides and salts) as well as sulfoximine compounds (e.g.
buthionin sulfoximines, homocystein sulfoximines, butionin
sulfones, penta-, hexa-, hepta-thionin sufoximine) in very small
compatible doses (e.g. pmol to .mu.mol/kg), further (metal)
chelating agents (e.g. .alpha.-hydroxy fatty acids, palmitic acid,
phytinic acid, lactoferrine), .alpha.-hydroxy acids (e.g. citric
acid, lactic acid, malic acid), humin acid, gallic acid, gallic
extracts, bilirubin, bifiverdin, EDTA, EGTA and their derivatives,
unsaturated fatty acids and their derivatives (e.g.
.gamma.-linolenic acid, linolic acid, oleic acid), folic acid and
their derivatives, ubichinon and ubichinol and their derivatives,
vitamin C and derivatives (e.g. ascorbyl palmitate, Mg-ascorbyl
phosphate, ascorbyl acetate), tocopheroles and derivatives (e.g.
vitamin E acetate), vitamin A and derivatives (vitamin A patmitate)
as well as koniferyl benzoate of benzoe resin, rutinic acid and
their derivatives, .alpha.-glycosylrutin, ferula acid, furfuryliden
glucitol, carnosine, butylhydroxy toluene, butylhydroxy anisol,
nordihydro guajak resin acid, nordihydro guajaret acid, trihydroxy
butyrophenon, uric acid and their derivatives, mannose and its
derivatives, super oxide dismutase, zinc and its derivatives (e.g.
ZnO, ZnSO.sub.4), selen and its derivatives (e.g. selen-methionin),
stilbenes and their derivatives (e.g. stilben oxide, trans-stilben
oxide) and the derivatives suitable according to the invention
(salts, esters, ethers, sugars, nucleotides, nucleosides, peptides
and lipids) of these mentioned active substances.
For improvement of the flow properties further hydrotropes, such as
for example ethanol, isopropyl alcohol, or polyols can be used.
Polyols which in this case can be used preferably have 2 to 15
carbon atoms and at least two hydroxyl groups. The polyols can
further contain additional functional groups, especially amino
groups, or be modified with nitrogen. Typical examples are:
Glycerol; alkylen glycols, such as for example ethylene glycol,
diethylene glycol, propylene glycol, butylene glycol, hexylene
glycol as well as polyethylen glycols with an average molecular
weight from 100 to 1000 Daltons; oligoglycerol mixtures of
technical quality with a self-condensation degree of 1.5 to 10,
such as e.g. technical quality diglycerol mixtures with a
diglycerol content of 40 to 50% by weight; methyol compounds, such
as especially trimethylol ethane, trimethylol propane, trimethylol
butane, pentaerythrite and dipentaerythrite; low alkyl glucosides,
especially such with 1 to 8 carbons in the alkyl residue, such as
for example methyl and butyl glucoside; sugar alcohols with 5 to 12
carbon atoms, such as for example sorbitol or mannit; sugars with 5
to 12 carbon atoms, such as for example glucose or saccharose;
aminosugars, such as for example glucamine; dialcoholamines, such
as diethanolamine or 2-amino-1,3-propanediol.
As preservatives for example phenoxyethanol, formaldehyde solution,
parabene, pentanediol or sorbic acid as well as those mentioned in
enclosure 6, parts A and B of the cosmetic regulation, are further
classes of substances. As insect repellents
N,N-diethyl-m-toluamide, 1,2-pentanediol or insect repellent 3535
come into question, as self tanning agent dihydroxyaceton is
suited.
As perfume oils mixtures of natural and synthetic scent substances
should be mentioned. Natural scent substances are extracts of
flowers (lilies, lavendel, roses, jasmin, neroli, ylang-ylang),
stems and blades (geranium, patchouli, petitgrain), fruits (anis,
coriander, caraway, juniper), fruit shells (bergamot, lemon,
orange), roots (macis, angelica, celery, kardamon, costus, iris,
calmus), wood (stone pine, sandel, guajac, cedar, rosewood), herbs
and grass (tarragon, lemongrass, sage, thyme), needles and twigs
(spruce, fir, pine, traipsed), resins and balsams (galbanum, elemi,
benzoe, myrrh, olibanum, opoponax). Raw materials from animals are
also possible, such as for example zibet and castoreum. Typical
synthetic odour compounds are products from types of esters,
ethers, aldehydes, ketones, alcohols and hydrocarbons. Odour
compounds from types of esters are e.g. benzyl acetate,
phenoxyethyl isobutyrate, p-tert.butylcyclohexyl acetate, linalyl
acetate, dimethylbenzylcarbinyl acetate, phenylethyl acetate,
linalyl benzoate, benzyl formate, ethylmethylphenyl glycinate,
allylcyclohexyl propionate, styrallyl propionate and benzyl
salicylate. Benzylethyl ether belongs for example to the ethers, to
the aldehydes e.g. the linear alkanales with 8 to 18 carbon atoms,
citral, citronellal, citronellyl oxyacetaldehyde, cyclamen
aldehyde, hydroxy citronellal, lilial and bourgeonal, to the
ketones e.g. the ionones, .varies.-isomethyl ionon and methylcedryl
ketone, to the alcohols anethol, citronellol, eugenol, isoeugenol,
geraniol, linalool, phenylethyl alcohol and terpineol; to the
hydrocarbons mainly the terpenes and balsams belong. However,
mixtures of different odour substances are preferred, which
together give a pleasant smell. Also etheral oils with low
volatility, which often are used as aroma components, are suited as
perfume oils, e.g. sage oil, chamomile oil, carnation oil, melissa
oil, mint oil, cinnamon leaf oil, limeflower oil, juniper berry
oil, vetiver oil, oliban oil, galbanum oil, labolanum oil and
lavandin oil. Preferably used are bergamot oil, dihydromyrcenol,
lilial, lyral, citronellol, phenylethyl alcohol,
.alpha.-hexylcinnamon aldehyde, geraniol, benzylaceton, cyclamen
aldehyde, linalool, boisambrene forte, ambroxane, indol, hedione,
sandelice, lemon oil, mandarin oil, orangenoil, allylamyl
glycolate, cyclovertal, lavandine oil, muskateller sage oil,
.beta.-damascone, geranium oil bourbon, cyclohexyl salicylate,
vertofix coeur, iso-E-super, fixolide NP, evemyl, iraidein gamma,
phenylacetic acid, geranyl acetate, benzyl acetate, rose oxide,
romillate, irotyl and floramate, alone or in mixtures.
As colouring agents such substances which are suited and approved
for cosmetic purposes can be used, such as for example those
mentioned in the publication "Kosmetische Farbemittel" (cosmetic
dyes) of the "Farbstoffkommission der Deutschen
Forschungsgemeinschaft", published by Verlag Chemie, Weinheim,
1984, p. 81-106. These dyes are generally used in concentrations
from 0.001 to 0.1% by weight, based on the whole mixture.
Typical examples of germ inhibiting substances are preservatives
with specific effects against gram-positive bacteria, such as
2,4,4'-trichloro-2'-hydroxy diphenylether, chlorohexidin
(1,6-di-(4-chlorophenyl-biguanido-hexan) or TCC
(3,4,4'-trichlorocarbanilide). Many scent substances and etheral
oils also have antimicrobial properties. Typical examples are the
active agents eugenol, menthol and thymol in carnation, mint and
thyme oil. An interesting natural deo substance is the terpene
alcohol famesol (3,7,11trimethyl-2,6,10-dodecatrien-1-ol), which is
present in lime flower oil and has a smell of lilies of the valley.
Also glycerol monolaurate have been used as bacteriostaticum.
Normally the content of the further germ inhibiting agent is about
0.1 to 2% by weight--based on the solids content of the
preparations.
The cumulative contents of the auxiliary and additional agents can
be 1 to 50, preferably 5 to 40% by weight, based on the agents. The
manufacture of the agents can take place by common cold or hot
processes; preferably the work is carried out according to the
phase inversion temperature method.
EXAMPLES
A panel consisting of 15 female probands aged between 35 and 50
years were during a time period of 28 days daily exposed to a daily
exposition of different glucans. For this purpose O/W skin cremes
with the composition stated in table 1 was made by mixing of the
phases I and II at 95.degree. C.
TABLE 1 Composition of O/W Skin Cremes Composition Phase I Phase II
Cetylstearyl alcohol 8.0 -- Ceteareth-12 1.5 -- Ceteareth-20 1.5 --
Cetearyl isononanoate 15.0 Paraffin oil, viscous 5.0 Baysilon oil M
300 5.0 Glucan 20.0 Glycerol 6.0 Water -- 38.0 Sum 36.0 64.0
The probands used the skin cremes daily before going to bed. With
intervals of 7 days the number, depth and lenght of the skin
wrinkles were determined for each of the participants by means of
profilometry of a selected part of the skin, i.e. a vertcal stripe
of 2 cm width and 5 cm length, having an upper left and right
boundary. which occurs if from the nose root a horizontal line is
drawn, from this and against the right eye 2, respectively 4 cm,
are cleared away and both resulting points in each case are
elongated in an angle of 270.degree. in each case 2 cm. The
dimensionless product of depht, number and lenght of the skin
wrinkles on the day before the beginning of the exposure was set as
standard (=100%), and all the following measurements were related
to this. At the same time the skin roughness of the pro-bands was
evaluated on a scale from 0 ="unchanged" to 3="strongly improved".
The results are summarized in table 2. Example 1 is according to
the invention, the examples V1 to V7 are for comparison. It can be
seen that the water soluble .beta.-(1,3) glucans of the invention,
which have no (1,6) linkages, exhibit a better effect than known
glucans according to the state of the art.
TABLE 2 Skin ageing and Skin Roughness Skin ageing after [d] in [%]
Skin ageing after [d] Ex. Glucan 0 7 14 21 28 0 7 14 21 28 1
.beta.-1,3 Glucan 100 96 91 85 79 0 1 2 3 3 V1 Schizophyllan.sup.1)
100 98 95 90 86 0 0 1 2 3 V2 Krestin.sup.3) 100 99 96 92 88 0 0 0 1
2 V3 Sclereoglucan.sup.4) 100 100 99 96 88 0 0 0 1 2 V4
CM-Glucan.sup.5) 100 100 99 96 95 0 0 0 1 1 V5 Mannozym.sup.6) 100
100 100 99 98 0 0 0 1 1 V6 Lichenin.sup.7) 100 100 100 100 98 0 0 0
0 1 V7 Isolichenin.sup.8) 100 100 100 100 98 0 0 0 0 1 Legend:
.sup.1) Highcareen .RTM. GS, Henkel KGA Dusseldorf
.sup.2).beta.-(1,3)-/.beta.-(1,6) Glucan, extract from
Schizophyllum Commune .sup.3).beta.-(1,3)-.beta.-(1,4)-.beta.(1,6)
Glucan-protein (30%) complex, extract from Conolossus versicolor
.sup.4).beta.-(1,3)/.beta.-(1,6) Glucane, Extract from Sclereoticum
glucanium .sup.5) Carboxymethylated .beta.-(1,3) glucan, extract
from Saccharomyces cervisiae .sup.6).alpha.-Mannene with branches,
extract from Saccharomyces cervisiae
.sup.7).beta.-(1,3)/.beta.-(1,4) Glucan +
.alpha.-(1,3)/.alpha.-(1,4) glucan mixture, extract from Cetraria
islandica (extract of lichen)
* * * * *